Asthma is a common disease and a significant public health problem, affecting one in every 10 individuals, nearly 30 million people in the US alone. About 5-10% of asthmatics have severe disease that is difficult to control with standard therapies. Severe asthmatics are considered to be relatively resistant to corticosteroids, a mainstay of therapy in asthma. Furthermore, chronic corticosteroid therapy often results in side effects that adversely affect outcomes. Thus, more effective treatment options, which are safe, cost-effective and easy to administer, are needed for severe asthmatics. A better understanding of the different factors that contribute to disease severity and pathogenesis will be necessary to identify new, personalized treatment and management approaches for severe asthmatics. Our goal is to gain a better understanding of the pathogenic mechanisms that differentiate severe asthma from mild to moderate asthma. In so doing, we hope to discover novel pathways that can be manipulated to achieve our primary aim of developing new therapies for severe asthmatics.